Wedelolactone attenuates cerebral ischemia-reperfusion injury by blocking GPX4-mediated ferroptosis

Abstract

Cerebral ischemia is currently the third leading cause of death worldwide. Among its complications, cerebral ischemia-reperfusion (I/R) is considered the most inevitable problem. To address this condition, there is a need for the development of more drugs. Wedelolactone, the main active chemical component extracted from dried lotus leaves, exhibits a wide range of pharmacological effects. Here we constructed an oxygen-glucose deprivation/reperfusion (OGD/R) model. Cell counting kit-8 (CCK-8) assays evaluated the impact of Wedelolactone on cell growth. Real-time quantitative polymerase chain reaction (RT-qPCR) assessed its effects on inflammation. We employed 2′,7′-Dichlorofluorescein (DCF) staining and an iron detection kit to measure ferroptosis. Flow cytometry (FCM) and immunoblot assays were utilized to investigate cell apoptosis. The results showed that Wedelactone promoted OGD-induced HT-22 cell viability and alleviated OGD/R-induced cellular inflammation, OGD/R-stimulated ferroptosis and OGD/R-induced apoptosis. Mechanically, Wedelactone inhibited OGD/R-stimulated ferroptosis via mediating glutathione peroxidase 4 (GPX4) expression. In conclusion, Wedelolactone may attenuate cerebral ischemia-reperfusion (CIR)/I by blocking GPX4-mediated ferroptosis.